相关实验视频
Updated: May 9, 2026
14:57
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
在体内激活p53瘤抑制路由由工程循环化物
Yanbin Ji1, Subhabrata Majumder2, Melissa Millard1
1Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033, USA.
Journal of the American Chemical Society
|July 16, 2013
概括
改造的环酸向Hdm2和HdmX,抑制癌细胞的存活. 这种新型的MCo-PMI显示出对野生型p53瘤的稳定性和有效性,提供了有前途的癌症治疗方法.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 过度表达Hdm2和HdmX会使癌细胞中的p53瘤抑制路径失活.
- 向Hdm2/HdmX是野生型p53癌症的治疗策略.
- 模仿p53的线性是强大的Hdm2/HdmX对手,但稳定性和生物可用性较差.
研究的目的:
- 为了设计循环MCoTI-I作为Hdm2/HdmX的稳定和生物可用对手,用于癌症治疗.
- 评估工程化环胺MCo-PMI在对抗p53降解及其对癌细胞的细胞毒性作用中的有效性.
主要方法:
- 设计了循环MCoTI-I支架,以创建MCo-PMI.
- 评估MCo-PMI与Hdm2和HdmX的结合亲和力.
- 在人类血清中评估MCo-PMI稳定性.
- 试验MCo-PMI的细胞毒性和p53通路激活在野生类型的p53癌症细胞系体外和体内.
主要成果:
- 设计的环氧化物MCo-PMI证明了对Hdm2和HdmX的纳米分子结合亲和力较低.
- 在人类血清中,MCo-PMI表现出高稳定性.
- MCo-PMI对野生型p53癌细胞系具有细胞毒性.
- 在体外和体内,MCo-PMI激活了p53瘤抑制途径.
结论:
- 环胺MCoTI-I是开发Hdm2/HdmX抗剂的有效支架.
- 通过稳定p53通路,MCo-PMI代表了治疗野生类型p53癌症的有希望的治疗候选者.
- 工程循环可以克服线性的局限性,以准细胞内蛋白质-蛋白质相互作用.
相关概念视频
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
02:36DNA Damage can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
02:36DNA Damage Can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
02:34Inhibition of Cdk Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
01:31The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
01:23Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.